Sexual differentiation of the brain in male mammals is dependent upon testicular production of testosterone (T). In the laboratory rat this process occurs perinatally. A surge of T on embryonic days 18/19 appears to sensitize the hypothalamus to exposure of T postnatally. The mechanism of action of this embryonic surge of T and its regulation are basically unknown. With respect to the latter, there is some evidence that at least the earliest secretion of T by the Leydig cells of the testes is independent of other factors and is possibly programmed genetically. However, even "programmed" genetic events are subject to modification. The objective of the present study is to determine whether or not the maternal hormonal environment plays any role in the prenatal events which lead eventually to the sexual differentiation of the brain. Pregnant female rats will be hypophysectomized on embryonic day 13, or sham hypophysectomized. In an attempt to identify purely fetal/maternal interactions, half the male and female pups will be gonadectomized on the day of birth or sham gonadectomized. At 50 days of age the experimental rats will be sacrificed and their brains removed and processed histologically. The volume of the sexual dimorphic nucleus of the preoptic area (SDN-POA), which is normally greater in the male rat, and that of the anteroventral periventricular nucleus (AVPV), which is normally greater in the female rat, will be determined. It is hypothesized that hypophysectomy of the pregnant female will inhibit the development of the SDN-POA in males but increase AVPV volume. Potential effects on the female are more difficult to predict because there is evidence both for the hormone- independent development of the female rat brain and its dependence on some exposure to gonadal hormones. The demonstration of a maternal contribution to the sexual differentiation of the fetal brain would be of considerable importance to our understanding of the fundamental concept of the sexual differentiation of the brain in mammal presumably including human beings.